Case-specific potentiation of glioblastoma drugs by pterostilbene
| Autor: | Ludmila Elfineh, Ulf Martens, Ida-Maria Sintorn, Shimei Wee, Narendra Padhan, Sathishkumar Baskaran, Linnéa Schmidt, Maria Häggblad, Karin Forsberg-Nilsson, Bengt Westermark, Patrik Johansson, Ingrid Lönnstedt, Michael Andäng, Lydia C. Green, Lene Uhrbom, Sven Nelander, Lena Claesson-Welsh, Bo Lundgren, Damian J. Matuszewski, Cecilia Krona |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pterostilbene Cell Pharmacology stilbenoids chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols Stilbenes EGFR inhibitors Aged 80 and over drug repurposing Brain Neoplasms Cell Cycle Drug Synergism Gefitinib Middle Aged Cell cycle Phenotype medicine.anatomical_structure Oncology Gene Knockdown Techniques Chromosomal region Female TXNIP Research Paper medicine.drug DNA Copy Number Variations MAP Kinase Signaling System cancer therapeutics 03 medical and health sciences Cell Line Tumor medicine glioblastoma initiating cells Humans Protein Kinase Inhibitors Aged Cell Proliferation Cell growth business.industry Gene Expression Profiling glioblastoma Antineoplastic Agents Phytogenic 030104 developmental biology chemistry Mutation Quinazolines Transcriptome business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.12298 |
| Popis: | Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients. |
| Databáze: | OpenAIRE |
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